One major impetus for using phenyltropane analogs of cocaine for PET and SPECT imaging is to detect Parkinson's disease in its preclinical phase, to follow disease progression and the efficacy of prophylactic therapy and monitor tissue transplants. We and others have reported the favorable properties of -carbomethoxyaryltropanes (WIN 35,428 or CFT and analogs) for brain imaging. The present study extends the evaluation of phenyltropanes to an unusual structure, (S)-(+)-2 -carbomethoxy-3a-[bis(4-fluorophenyl)methoxy] tropane [11C]difluoropine), a potent (IC50 = 10.9 nm) and selective (dopamine:serotonin transporter binding affinity ratio 324) for the dopamine transporter. The compound was labeled with [11C] by direct methylation of the normethyl precursor with [11C] CH3, followed by HPLC purification (>30% yield, specific activity >800 mCi/fmol, radiochemical purity > 98%). Its tracer kinetics were evaluated in normal monkey brain. After injection of 5-7 mCi of [11C]difluoropine there was fast accumulation in different regions of the brain. While activity washed out from all brain regions after initial accumulation, the caudate and putamen regions continued to accumulate activity during the 90-min imaging session. The caudate-putamen to cerebellum ratios were 1.5 and 2.2 at 45 and 90 min.,